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New insights into Bovine Leukemia Virus (BLV) transcriptional regulation

par Bellefroid, Maxime ;Plant, Estelle ;Rodari, Anthony ;Van Driessche, Benoît ;Fauquenoy, Sylvain ;Vanhulle, Caroline ;Nestola, Lorena ;Burny, Arsène ;Van Lint, Carine
Référence Frontiers In Retrovirology (11-13 Septembre 2018: Leuven, Belgium)
Publication Non publié, 2018-09-12

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Résumé :

Bovine leukemia virus (BLV) is a B-lymphotropic oncogenic deltaretrovirus infecting cattle and closely related to human T-cell leukemia viruses I and II (HTLV-I and II). Despite the well-established repression of the 5'LTR-driven viral gene expression, we and others have discovered and characterized two alternative viral promoters[1][2][3][4], allowing a high expression of viral miRNAs[2][3] and antisense viral transcripts[4], potentially contributing to tumor progression and to escape from the host immune system. In addition, our data have suggested a collision phenomenon between the RNAPIII transcribing the miRNA cluster and the RNAPII coming in an antisense orientation from the 3’LTR[1] with, as a result, a stalling of both RNA polymerase complexes. These latter results have indicated that transcriptional interference could be seen as a new mechanism used by BLV to regulate its three transcriptional activities.In this work, we investigated the interplay and self-regulation between the three BLV promoter activities and showed putative critical functions of the transcriptional interference to drive or repress BLV transcriptional activities. In addition, we highlighted the implication of new transcription factors in BLV transcriptional and epigenetic regulations but also in BLV-mediated pathogenesis. Overall in this study, we further investigated new alternative ways used by BLV to regulate its transcriptional and epigenetic status and provided new fundamental insights into BLV transcriptional and epigenetic regulations which could explain the escape from the host immune system and/or the BLV-induced pathogenesis.References[1] B. Van Driessche, A. Rodari, N. Delacourt, S. Fauquenoy, C. Vanhulle, A. Burny, O. Rohr and C. Van Lint, Characterization of new RNA polymerase III and RNA polymerase II transcriptional promoters in the Bovine Leukemia Virus genome, Sci Rep 6, 2016, 31125-31139[2] N. Rosewick, M. Momont, K. Durkin, H. Takeda, F. Caiment, Y. Cleuter, C. Vernin, F. Mortreux, E. Wattel, A. Burny, M. Georges, and A. Van den Broeke, Deep sequencing reveals abundant noncanonical retroviral microRNAs in B-cell leukemia/lymphoma, Proc Natl Acad Sci USA 110, 2013, 2306–2311.[3] R. P. Kincaid, J. M. Burke, C. S. Sullivan, RNA virus microRNA that mimics a B-cell oncomiR, Proc Natl Acad Sci USA 109, 2012, 3077-3082.[4] K. Durkin, N. Rosewick, M. Artesi, V. Hahaut, P. Griebel, N. Arsic, A. Burny, M. Georges and A. Van den Broeke, Characterization of novel Bovine leukemia Virus (BLV) antisense transcripts by deep sequencing reveals constitutive expression in tumors and transcriptional interaction with viral a microRNAs, Retrovirology 13:33, 2016.